1. Technical Field
The present invention relates to the use of compositions to be orally administered for the treatment of osteoarthritis and pain associated to it. Additionally, the present invention relates to the use of compositions in the preparation of food or food supplements for nourishing the synovial fluid.
2. Related Art
Osteoarthritis is a degenerative joint disease which affects most people from the age of 65.
Osteoarthritis can be defined as the degeneration of the hyaline articular cartilage. Secondarily, the synovial membrane and the subchondral bone (bone in contact with the cartilage) are affected, and new bone is formed on the margins of joint surfaces.
The cartilage allows bones to move, by sliding over one another. It also absorbs tensions generated by physical movement. In osteoarthritis, the cartilage surface breaks and wears out, causing bones to move against each other, causing friction, pain, swelling and loss of articular mobility. With time, the joint may deform.
Under normal conditions, cartilage renewal is a very slow process, which consists of a constant synthesis (anabolism) and degradation (catabolism) of components of the extracellular matrix. The chondrocyte is the cell responsible for this metabolism, which must be perfectly coordinated.
Although the ethiology of osteoarthritis is still unknown, it is nowadays generally accepted that the first alterations occur at the chondrocyte level, eventually leading to a joint affected by osteoarthritis.
Several risk factors for osteoarthritis have been described, namely, age, inheritance, obesity, excess weight related disorders, sport-related physical stress, injuries or traumatisms, work activity and bone mineral density.
There is no definitive treatment for osteoarthritis. We highlight the following current options for therapy:
Symptomatic-action drugs which have a rapid action. Among these are: analgesics, nonsteroidal anti-inflammatory drugs (NSAIDs), corticoids and cyclooxygenase 2 (COX-2) selective inhibitors. The use of some of these drugs involves a high risk of potentially severe side effects, such as gastrointestinal problems derived from the use of NSAIDs.
Symptomatic-action drugs which act in a slower manner. These are better known as SYSADOA (Symptomatic Slow-Acting Drug for Osteoarthritis) (M. G. Lequesne, Rev. Rhum. (Eng./Ed.) 61;69-73 (1994); B. F. Leeb et al., J. Rheumatol. 27:205-211 (2000)). These substances include hyaluronic acid, chondroitin sulphate, glucosamine hydrochloride and the so-called glucosamine sulphate. This group of drugs is characterized by general efficacy similar to that of NSAIDs and also by greater safety and a more prolonged action, even a few months after treatment suspension (carry-over or residual effects). A number of clinical assays with hyaluronic acid (M. Dougados Semin. Artritis. Rheum. 30(2 Suppl. 1):19-25 (2000)) and with chondroitin sulphate (D. Uebelfart et al., Osteoarthritis Cart. 12:269-276 (2004)) have shown that both compounds, as well as acting as SYSADOA, may have an influence on the course of osteoarthritis, either by slowing its progress or by delaying its onset, by acting as S/DMOAD drugs (Structure/Disease Modifying anti-Osteoarthritis Drug).
Hyaluronic acid is a naturally occurring non-sulphated glycosaminoglycan with a polymeric structure of disaccharides of N-acetyl-D-glucosamine and D-glucuronic acid. It is extracted mainly from organs or tissues of birds and mammals. It is one of the primary components of cartilages, synovial membranes and synovial fluid. The endogenous hyaluronic acid is primarily synthesised by synoviocytes, in addition to, although to a lesser extent, by chondrocytes. In osteoarthritis patients, the synovial fluid shows a lower concentration of endogenous hyaluronic acid; therefore, the lubricant effect and the viscoelastic properties of the synovial fluid are reduced, since the synovial fluid, being a viscous fluid present in the joint cavity, lubricates and nourishes the joint cartilage, thus reducing the friction between the joint surfaces, and facilitating movement of the joint. The preferred route for administration of hyaluronic acid in the treatment of osteoarthritis is intra-articular. The action of intra-articular hyaluronic acid lies in the improvement of the mobility of joints having a degenerate cartilage surface and synovial fluid alterations.
Hyaluronic acid is also used in the field of intra-articular implants, in ophthalmology, for accelerating the healing of wounds, and in cosmetics.
Dermatan sulphate, otherwise known as chondroitin sulphate B, is a naturally occurring glycosaminoglycan with a polymer structure primarily comprising disaccharides of sulphated N-acetyl-D-galactosamine and L-iduronic acid. Several disaccharide units contain N-acetyl-D-galactosamine lacking sulphate groups, or substitutions of L-iduronic acid for D-glucuronic acid. It is obtained from organs or tissue of birds and mammals.
Dermatan sulphate is used, mixed with other glycosaminoglycans, for the treatment of thromboses by the subcutaneous route, and in the manufacturing of cosmetics.
Collagen hydrolysate comprises a mixture of aminoacids and low molecular weight peptides. It is obtained through the controlled enzymatic hydrolysis of collagenous protein in skin and other conjunctive tissues. It is primarily used in cosmetics.
U.S. Patent Application Publication No. 2005/0084518 describes a health food containing hyaluronic acid and dermatan sulphate. This food differs from the compositions in this invention in that it is useful for skin embellishment.
In U.S. Patent Application Publication No. 2002/0068718 the use of orally administered hyaluronic acid in the treatment for osteoarthritis is described. Chondroprotective compositions containing hyaluronic acid are also described. In addition to hyaluronic acid, the compositions may contain glucosamine sulphate and/or chondroitin sulphate.
U.S. Pat. No. 6,607,745 describes a food supplement essentially consisting of hyaluronic acid for ameliorating articular pain and other malaise associated to osteoarthritis.
The problem to be solved by the present invention is to provide a composition more efficacious than hyaluronic acid for treating osteoarthritis and osteoarthritis-associated pain, for nourishing the joint and for improving articular mobility.
To date, no description can be found of the use of a composition comprising hyaluronic acid and dermatan sulphate in the treatment, prevention or prophylaxis of osteoarthritis or osteoarthritis-associated articular pain.
Furthermore, to date no description can be found of the use of a composition comprising hyaluronic acid and dermatan sulphate in the manufacturing of a food or food supplement for the nourishment of a joint, particularly for the nourishment of the synovial fluid present in the joint, o for improving the articular mobility.